title: In vitro cytocidal effects of the essential oil from Croton cajucara (red sacaca) and its major constituent 7- hydroxycalamenene against Leishmania chagasi.
abstract: BACKGROUND
  Visceral leishmaniasis is the most serious form of leishmaniasis and can be lethal if left untreated. Currently available treatments for these parasitic diseases are frequently associated to severe side effects. The leaves of Croton cajucara are used as an infusion in popular medicine to combat several diseases. Previous studies have demonstrated that the linalool-rich essential oil from C. cajucara (white sacaca) is extremely efficient against the tegumentary specie Leishmania amazonensis. In this study, we investigated the effects of the 7-hydroxycalamenene-rich essential oil from the leaves of C. cajucara (red sacaca) against Leishmania chagasi, as well as on the interaction of these parasites with host cells.
  
  
  METHODS
  Promastigotes were treated with different concentrations of the essential oil for determination of its minimum inhibitory concentration (MIC). In addition, the effects of the essential oil on parasite ultrastructure were analyzed by transmission electron microscopy. To evaluate its efficacy against infected cells, mouse peritoneal macrophages infected with L. chagasi promastigotes were treated with the inhibitory and sub-inhibitory concentrations of the essential oil.
  
  
  RESULTS
  The minimum inhibitory concentrations of the essential oil and its purified component 7-hydroxycalamenene against L. chagasi were 250 and 15.6 μg/mL, respectively. Transmission electron microscopy analysis revealed important nuclear and kinetoplastic alterations in L. chagasi promastigotes. Pre-treatment of macrophages and parasites with the essential oil reduced parasite/macrophage interaction by 52.8%, while it increased the production of nitric oxide by L. chagasi-infected macrophages by 80%.
  
  
  CONCLUSIONS
  These results indicate that the 7-hydroxycalamenene-rich essential oil from C. cajucara is a promising source of leishmanicidal compounds.
authors.affiliation: Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes/UFRJ, 21941-590 Rio de Janeiro, RJ, Brazil. abvermelho@micro.ufrj.br.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Rodrigues
authors.forename: Mariana M B
authors.initials: MM
authors.lastname: Azevedo
authors.forename: Francisco C M
authors.initials: FC
authors.lastname: Chaves
authors.forename: Humberto R
authors.initials: HR
authors.lastname: Bizzo
authors.forename: Suzana
authors.initials: S
authors.lastname: Corte-Real
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Alviano
authors.forename: Celuta S
authors.initials: CS
authors.lastname: Alviano
authors.forename: Maria S S
authors.initials: MS
authors.lastname: Rosa
authors.forename: Alane B
authors.initials: AB
authors.lastname: Vermelho
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D029802:Croton / Q000737:chemistry*; D005260:Female; D007891:Leishmania / Q000187:drug effects*; D008018:Life Cycle Stages / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000378:metabolism; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000032:analysis / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C520676:7-hydroxycalamenene; D000981:Antiprotozoal Agents; D009822:Oils, Volatile; D010936:Plant Extracts; D012717:Sesquiterpenes; D009569:Nitric Oxide; D010447:Peptide Hydrolases